This application requests support for the Clinical Studies component of the NIMH Clinical REsearch BRanch Collaborative Program on the Psychobiology of Depression. The Collaborative Program proposes to comprehensively investigate the biological, genetic and clinical aspects of the nature and etiology of the depressive disorders. The collaborative rtudies program initially began in 1971 with a consensus of its Advisory body that the program should be addressed to three major substantive areas: 1) Nosology: An evaluation of the comparative validity of alternative systems for clinical classification; 2) Genetics: An evaluation of the validity of the several hypotheses that genetic factors are involved in the evolution of some types of depressive disorders; and 3) Pathophysiology: A further evaluation of several promising psychobiological findings in an attempt to arrive at some preliminary conceptual hypotheses regarding the pathophysiology of these illnesses. It soon became clear, however, that an ever broader investigational approach to the analysis of the critical clinical and psychological issues underlying depression would be necessary. Over the course of the development of the current set of protocols, the Clinical Studies Committee has therefore broadened its scope to include the testing of critical hypotheses relative to the effects of environmental events and the role of personality in influencing the nature of the disorders, and to provide a comprehensive description of the depressed state in its multiple aspects. The aims and hypotheses to be tested in the Clinical Studies Research Program will be set out in a series of protocols which deal with the following themes: 1) Comparative Nosology; 2) The Genetic Bases of Depression; 3) The Role of Life Events and Environmental Stress; 4) The Relationship of Premorbid Personality to Clinical Depression; 5) Phenomenology of Depression; 6) Follow-up Studies. Each of these areas involve current controversy among laboratory investigations, clinical researchers and theoreticians. The research design and procedures have been chosen to generate data which will test critical hypotheses. Important theoretical and clinical issues which remain unresolved in each of these areas.